Our work is focussed on the molecular mechanisms responsible for establishing and maintaining stable states of gene expression during vertebrate embryogenesis. Progress has been achieved in the following key areas: 1. We have found that histones can exert dominant repressive effects on the transcription of a gene in vivo in spite of an abundance of transcription factors for that gene. 2. We have determined that the temporal regulation of transcription during early embryogenesis will depend upon the capacity of a specific transcription factor to bind to DNA in the presence of core histones and to recruit TBP to a promoter in a competition for binding with the core histones. 3. We have found that the deformation of DNA by the core histones increases its utilization by the human immunodeficiency virus (HIV) integrase. 4. We have discovered that the translation process is functionally coupled to transcription in eukaryotes. 5. We have demonstrated that the nuclear proteins RCC1 and Ran are directly involved in signal transduction pathways preventing the initiation of premature mitosis. 6. We have characterized thyroid hormone response elements in the gene encoding the thyroid hormone receptor. 7. We have found that the morphogen hedgehog is reputated by thyroid hormone during metamorphosis.